Our program addresses the hypothesis that with growth and development there are changes in the normal electrophysiologic, autonomic, biochemical and structural characteristics of the heart, which alter its responses to pathological processes and to pharmacologic agents. We believe that the changes in expression of disease processes and the responses of the heart to potentially therapeutic interventions that occur developmentally are conditioned in part by the developmental stage of the end organ (the heart) as well as by these structures that influence the heart (autonomic nervous system and hormones) and by those processes that control drug interactions with the heart. Hence the theme focuses on a developmental approach to cardiac arrhythmias and their therapy. The approach is multifaceted in that a variety of electrophysiologic, biophysical, biochemical, pharmacological, ultrastructural and cell culture techniques are used. The research is incorporated into 5 investigative units (housed in 4 "Projects") and the overall hypothesis tested recurs in the electrophysiological, biochemical and autonomic studies, as well as in Core C (ultrastructure and immunopathology). Two additional cores provide administrative (A) and tissue culture (B) support. Although the overall approach is to study growth and development through adult life, the most intensive area of investigation is centered on the neonatal and into stages. This is in keeping with our major interest in cardiovascular disease in the young. The significance of these studies is that they provide an alternative method to the standard approaches for considering arrhythmias, their genesis and treatment. Using the information obtained about developmental changes in function and structure we can not only improve our understanding of developmental changes in the mechanisms responsible for normal rhythm and arrhythmias but can design and seek new means for the prevention and treatment of arrhythmias.